Project Summary/Abstract The purpose of this K23 application is to further Dr. Adam Gerstenecker's academic research career in multiple sclerosis (MS) investigating cognitive impairment, financial and medical decisional capacity, and brain imaging. The candidate is a neuropsychologist whose long-term career goal is to develop a rehabilitation program for people who are at particular risk for financial and medical capacity compromise. The study of financial and medical decision-making capacity appears to have particular relevance in MS. For example, 50%- 75% of people with MS are no longer working a decade after diagnosis; thus, economic hardship and financial issues become imminent challenges in the lives of those with MS. As a result, budgets must be further stretched and investment planning retooled and reprioritized. These individuals also confront new questions regarding medical treatments while choosing among non-curative therapies that are associated with varying side effects. However, up to 65% of people with MS have cognitive impairment which can negatively affect their ability to make sound medical decisions. At present, there is only one published study examining capacity in MS and it has a number of limitations. In regards to neuroimaging, although previous studies have shown that diffusion imaging (DI) metrics are correlated with cognitive dysfunction in MS, studies examining the association between DI metrics and financial or medical capacity in MS are not available. The objective of this K23 application is to investigate financial and medical capacity in MS and to examine their clinical and neuroanatomic correlates. This project will provide preliminary data for future intervention studies in financial and medical capacity that will be the topic of a future R01 grant proposal. The specific research aims are to: (1) examine differences in financial and medical capacity between MS, TBI, and healthy controls; (2) examine the neurocognitive, demographic, and disease correlates of capacity in relapsing- remitting and progressive MS; and (3) establish correlations between DI metrics and capacity in MS. In addition, a number of mediational and moderational analyses will be conducted. This K23 will provide the essential training, protected time, and research data to ensure successful transition to independence including: (1) developing increased knowledge about the course, treatment, and clinical presentation of MS; (2) developing increased knowledge about legal and ethical issues in decision-making capacity and to gain increased proficiency in capacity-related grantsmanship; (3) gaining increased knowledge in neuroimaging procedures and the processing of neuroimaging data; (4) gaining increased knowledge in intervention research and design, with a focus on the development of tailored cognitive rehabilitation; and (5) receiving increased training in advanced statistical methods. The mentorship team is led by Dr. Khurram Bashir, an internationally recognized expert, mentor, and scientist in MS with an outstanding mentoring track record.